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    Tph1 tryptophan hydroxylase 1 [ Mus musculus (house mouse) ]

    Gene ID: 21990, updated on 11-Nov-2024

    Summary

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    Official Symbol
    Tph1provided by MGI
    Official Full Name
    tryptophan hydroxylase 1provided by MGI
    Primary source
    MGI:MGI:98796
    See related
    Ensembl:ENSMUSG00000040046 AllianceGenome:MGI:98796
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    Tph
    Summary
    This gene encodes a member of the biopterin-dependent aromatic amino acid hydroxylase family. The encoded protein is one of two tryptophan hydroxylase enzymes that catalyze the first and rate limiting step in the biosynthesis of the hormone and neurotransmitter, serotonin. This gene is expressed in peripheral organs, while tryptophan hydroxylase 2 is expressed in neurons. The encoded protein is involved in the development of hypoxia-induced elevations in pulmonary pressures and pulmonary vascular remodeling, and has also been implicated as a regulator of immune tolerance. Disruption of this gene is associated with cardiac dysfunction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2013]
    Expression
    Biased expression in colon adult (RPKM 1.2), duodenum adult (RPKM 0.5) and 8 other tissues See more
    Orthologs
    human all
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    Genomic context

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    See Tph1 in Genome Data Viewer
    Location:
    7 B3; 7 30.43 cM
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 7 NC_000073.7 (46294065..46321961, complement)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 7 NC_000073.6 (46644641..46672537, complement)

    Chromosome 7 - NC_000073.7Genomic Context describing neighboring genes Neighboring gene STARR-positive B cell enhancer ABC_E4927 Neighboring gene potassium voltage gated channel, Shaw-related subfamily, member 1 Neighboring gene secretion regulating guanine nucleotide exchange factor Neighboring gene predicted gene, 22969 Neighboring gene STARR-seq mESC enhancer starr_18863 Neighboring gene STARR-seq mESC enhancer starr_18865 Neighboring gene STARR-seq mESC enhancer starr_18866 Neighboring gene STARR-seq mESC enhancer starr_18867 Neighboring gene serum amyloid A-like 1 Neighboring gene serum amyloid A 3

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. D-methionine improves cisplatin-induced anorexia and dyspepsia syndrome by attenuating intestinal tryptophan hydroxylase 1 activity and increasing plasma leptin concentration.
      Title: D-methionine improves cisplatin-induced anorexia and dyspepsia syndrome by attenuating intestinal tryptophan hydroxylase 1 activity and increasing plasma leptin concentration.
    2. Protein acetylation derepresses Serotonin Synthesis to potentiate Pancreatic Beta-Cell Function through HDAC1-PKA-Tph1 signaling.
      Title: Protein acetylation derepresses Serotonin Synthesis to potentiate Pancreatic Beta-Cell Function through HDAC1-PKA-Tph1 signaling.
    3. Investigating the complex interplay between genotype and high-fat-diet feeding in the lactating mammary gland using the Tph1 and Ldlr knockout models.
      Title: Investigating the complex interplay between genotype and high-fat-diet feeding in the lactating mammary gland using the Tph1 and Ldlr knockout models.
    4. Interleukin-33 Induces the Enzyme Tryptophan Hydroxylase 1 to Promote Inflammatory Group 2 Innate Lymphoid Cell-Mediated Immunity.
      Title: Interleukin-33 Induces the Enzyme Tryptophan Hydroxylase 1 to Promote Inflammatory Group 2 Innate Lymphoid Cell-Mediated Immunity.
    5. Mast cell Tph1 promotes obesity and insulin resistance.
      Title: Genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance.
    6. Overexpression of tryptophan hydroxylase-1 (TPH-1), an enzyme involved in 5-methoxytryptophan synthesis, reduces renal injury by attenuating renal inflammation and fibrosis, whereas TPH-1 deficiency exacerbates renal injury and fibrosis by activating NF-kappaB and inhibiting Nrf2 pathways.
      Title: Identification of serum metabolites associating with chronic kidney disease progression and anti-fibrotic effect of 5-methoxytryptophan.
    7. Both gut-specific Tph1 knockout mice and liver-specific Htr2a knockout mice are resistant to high fat diet-induced hepatic steatosis, without affecting systemic energy homeostasis.
      Title: Serotonin signals through a gut-liver axis to regulate hepatic steatosis.
    8. Data suggest that central melanocortin-4 receptor (MC4-R) and tryptophan hydroxylase (TPH) are involved in the efferent neuronal control of the kidneys.
      Title: Delineation of the central melanocortin circuitry controlling the kidneys by a virally mediated transsynaptic tracing study in transgenic mouse model.
    9. Prolactin-induced Tph1 expression.
      Title: Expression mechanism of tryptophan hydroxylase 1 in mouse islets during pregnancy.
    10. Tph1-deficient mice fed a high-fat diet (HFD) are protected from obesity, insulin resistance and nonalcoholic fatty liver disease (NAFLD) while exhibiting greater energy expenditure by brown adipose tissue.
      Title: Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis.
    Submit: New GeneRIF Correction See all GeneRIFs (27)

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)

    Pathways from PubChem

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    General gene information

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    Markers

    Homology

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables iron ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables tryptophan 5-monooxygenase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables tryptophan 5-monooxygenase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables tryptophan 5-monooxygenase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    Process Evidence Code Pubs
    involved_in aromatic amino acid metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within bone remodeling IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in circadian rhythm IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within mammary gland alveolus development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of ossification IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of ossification ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in platelet degranulation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within positive regulation of fat cell differentiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of hemostasis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in response to immobilization stress IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in serotonin biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in serotonin biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in neuron projection IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    tryptophan 5-hydroxylase 1
    Names
    tryptophan 5-monooxygenase 1
    NP_001129556.1
    NP_001263301.1
    NP_033440.1
    XP_011249148.1
    XP_036008805.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001136084.2 → NP_001129556.1  tryptophan 5-hydroxylase 1 isoform 1

      See identical proteins and their annotated locations for NP_001129556.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same isoform (1).
      Source sequence(s)
      AC090122, AF273257, BC072582, BM932391
      Consensus CDS
      CCDS21280.1
      UniProtKB/Swiss-Prot
      P17532
      UniProtKB/TrEMBL
      Q3UK52
      Related
      ENSMUSP00000103296.3, ENSMUST00000107669.9
      Conserved Domains (1) summary
      TIGR01270
      Location:3 → 441
      Trp_5_monoox; tryptophan 5-monooxygenase, tetrameric

    2. NM_001276372.1 → NP_001263301.1  tryptophan 5-hydroxylase 1 isoform 2

      See identical proteins and their annotated locations for NP_001263301.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 3' coding region and 3' UTR, compared to variant 1. The resulting isoform (3) is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AF273257, AK157858, BC038864
      Consensus CDS
      CCDS71970.1
      UniProtKB/TrEMBL
      Q3TZH2
      Related
      ENSMUSP00000128107.2, ENSMUST00000168335.3
      Conserved Domains (2) summary
      cl01244
      Location:109 → 145
      arom_aa_hydroxylase; Biopterin-dependent aromatic amino acid hydroxylase; a family of non-heme, iron(II)-dependent enzymes that includes prokaryotic and eukaryotic phenylalanine-4-hydroxylase (PheOH), eukaryotic tyrosine hydroxylase (TyrOH) and eukaryotic tryptophan ...
      cl09141
      Location:22 → 94
      ACT; ACT domains are commonly involved in specifically binding an amino acid or other small ligand leading to regulation of the enzyme

    3. NM_009414.3 → NP_033440.1  tryptophan 5-hydroxylase 1 isoform 1

      See identical proteins and their annotated locations for NP_033440.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1). Both variants 1 and 2 encode the same isoform (1).
      Source sequence(s)
      AC090122, BC072582, BM932391
      Consensus CDS
      CCDS21280.1
      UniProtKB/Swiss-Prot
      P17532
      UniProtKB/TrEMBL
      Q3UK52
      Related
      ENSMUSP00000037752.8, ENSMUST00000049298.15
      Conserved Domains (1) summary
      TIGR01270
      Location:3 → 441
      Trp_5_monoox; tryptophan 5-monooxygenase, tetrameric

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000073.7 Reference GRCm39 C57BL/6J

      Range
      46294065..46321961 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_036152912.1 → XP_036008805.1  tryptophan 5-hydroxylase 1 isoform X1

      UniProtKB/Swiss-Prot
      P17532
      UniProtKB/TrEMBL
      Q3UK52
      Conserved Domains (1) summary
      TIGR01270
      Location:3 → 441
      Trp_5_monoox; tryptophan 5-monooxygenase, tetrameric

    2. XM_011250846.3 → XP_011249148.1  tryptophan 5-hydroxylase 1 isoform X2

      Conserved Domains (1) summary
      pfam00351
      Location:5 → 334
      Biopterin_H; Biopterin-dependent aromatic amino acid hydroxylase
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P17532.1 GenPept UniProtKB/Swiss-Prot:P17532

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